Assessment of Pharmacokinetics and Food Effect of AD‐109, a Novel Formulation of Rivaroxaban 18 mg

Rivaroxaban is an oral anticoagulant that requires food intake at high doses (15 and 20 mg) due to a pronounced food effect. AD-109 is a novel formulation of rivaroxaban 18 mg, designed to enhance oral bioavailability and mitigate the food effect. This study aimed to evaluate the pharmacokinetics (PKs) of AD-109 compared to the conventional formulation, Xarelto (Xarelto, rivaroxaban 20 mg) and the effect of food on the PK of AD-109. Two open-label, single-dose, two-period, two-sequence crossover studies were conducted. In Study 1, participants received a single dose of AD-109 and Xarelto under fed state, while in Study 2, participants received a single dose of AD-109 under fed and fasted state. Serial blood samples were collected up to 34 h post-dose and PK parameters were calculated by non-compartmental method. In both studies, 33 out of 36 volunteers completed the study. The geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) for the maximum plasma concentration (C_max) and area under the curve until the last measurable concentration (AUC_0-last) of rivaroxaban for AD-109 to Xarelto were 1.0466 (0.9961-1.0996) and 0.9450 (0.9094-0.9819), falling within the bioequivalence range of 0.8-1.25. The corresponding values of AD-109 in the fed to fasted state were 1.0475 (0.9789-1.1209) and 0.9795 (0.9371-1.0238), suggesting the systemic exposure was not substantially influenced by food intake. AD-109 (rivaroxaban 18 mg) demonstrated a PK profile comparable to that of Xarelto (rivaroxaban 20 mg) and effectively minimized the food effect on drug exposure.